The health care burden associated with treatment of chronic and burn wounds amounts to more than $25 billion annually in the U.S., involving 8.6 million patients. One recent advance in wound care has been the development of biologic dressings that contain animal-derived components such as collagen. Biologic dressings provide superior healing rates in burns and chronic wounds. Associated with their use, however, is a significant rate (up to 20%) of bacterial infection that results in increased healing time, patient pain, and treatment costs. Therefore, an unmet need with the potential to broadly advance wound care is the fabrication of biologic dressings that incorporate broad-spectrum antibacterial agents such as silver. Silver formulations are widely used in hospitals for treatment of wound infections. However, approaches used to incorporate stabilized forms of silver into conventional dressings cannot be adapted to biologic dressings because the chemical and physical processing involved compromises their structure and activity. To address these needs, Imbed Biosciences, Inc. is developing a platform technology that enables integration of molecularly-thin polymer films containing precise loadings of bioactive agents onto wound dressings and skin substitutes. In this Phase 1 proposal, Imbed will optimize this technology to integrate silver nanoparticles onto biologic wound dressings (the exemplar of which will be Biobrane(R), a leading biologic dressing) such that they inhibit bacterial colonization without compromising cellular growth and repair. The innovation in Imbed's approach includes: (i) the engineering of nanometer-thick polymer films impregnated with precise loadings of silver nanoparticles that exert antimicrobial activity without cytotoxicity; and (ii) transfer of polymer films containing silver nanoparticles onto biologic dressings without compromising their structure and bioactivity. Preliminary data shows that Imbed's silver nanoparticle-coating that releases concentrations of silver two orders of magnitude lower than those released from conventional silver dressings, when integrated on Biobrane(R), killed 99.9999% bacteria (6 log10) on its surface within 24 hr and prevented sepsis in experimentally infected wounds in mice. For this project, Imbed has assembled a highly accomplished team of researchers with substantial expertise in biomaterials (Agarwal and Abbott), microbiology (Czuprynski), animal wound models (McAnulty and Murphy) and clinical wound care (McAnulty, Murphy and Schurr). In this proposal, polymer films containing silver nanoparticles will be integrated on Biobrane(R). In Aim 1, silver loadings that lead to antimicrobial activity without cytotoxicity in in-vitro assays will be optimized. Aim 2 will provide safety and efficacy data in mice by identifying silver loadings that do not cause systemic toxicity, facilitate normal wound healing, and promote healing of model infected wounds. Completion of these aims will enable further commercialization discussions with customers and provide critical feasibility data for Phase 2 studies (to include a wider range of bacterial strains/wound models). PUBLIC HEALTH RELEVANCE: Wound management presents a huge economic and healthcare burden in the U.S. The research described in this SBIR application will lead to the realization of a new class of hybrid wound dressings that combine the benefits of biologic and antimicrobial wound dressings. The new wound dressings will expedite wound closure, reduce use of antibiotics, minimize dressing changes and nurse time, and lower patient pain, medication costs and length of hospital stays.